Among the various functional imaging techniques, SPECT maintains an important and growing role in the study of disease models in small animals as well as in patient care. Many SPECT-labeled imaging probes that have highly specific distributions with very little background are being used to measure a wide range of biological parameters of importance in small animals including substrate metabolism, blood flow, hypoxia, protein synthesis and receptor characteristics. The utility of this important modality has been significantly enhanced in recent years by the development of methods to image transgene expression in vivo. Furthermore, SPECT is capable of dual-isotope imaging for correlating two biological processes with a single imaging study. Recent demand for small animal SPECT has also been driven by the pharmaceutical industry, where in vivo quantification of biological processes to measure an agent's mechanism of action and its concentration at the site of action is necessary. Each of these applications requires excellent spatial resolution not only because of the small scale of the details to be imaged but also for demanding detection and estimation tasks. Simultaneously, high sensitivity is also essential, as it is critically important for reducing image acquisition time, improving temporal resolution, increasing throughput for patient/animal studies, and reducing patient dose. While new developments in CCD/scintillator-based SPECT detectors have addressed the resolution issue by demonstrating sub- 100 micron intrinsic spatial accuracies, a detector that can simultaneously provide high-resolution and high- sensitivity has not yet been realized. This is primarily due to the well-known efficiency-resolution tradeoff in current scintillators and the parallax errors arising from oblique 3-ray incidences in any scintillator. Thus, the development of a novel scintillator that can overcome the traditional efficiency-resolution tradeoff and implementation of methodologies to minimize parallax errors is crucial for realizing a truly high-resolution, high- sensitivity SPECT detector. To address these issues, we propose to develop a novel sensor based on a scintillator of a unique design, coupled to a very high spatial resolution readout. Specifically, the scintillator will provide very high spatial resolution and high-sensitivity for 3 energies typically used in SPECT imaging and will permit depth-of- interaction (DOI) estimation for every event. The high spatial resolution intrinsic to the readout sensor, along with the DOI information, will enable the detector to achieve extremely fine and uniform spatial resolution and high sensitivity, in a cost-effective manner. PUBLIC HEALTH RELEVANCE: The goal of the proposed research is to develop a very high performance, cost-effective sensor for small animal single photon emission computed tomography (SPECT) imaging. Among other benefits, SPECT studies are well suited to imaging radiolabeled antibodies and other substances that can be used to localize and characterize tumors in small animals and are well suited to the development of new radiolabeled agents for diagnosing and tracking the treatment of diseases in humans. The development of such a sensor will significantly improve the resolution and sensitivity with which measurements can be made, and this, in turn, will allow the development of superior methods, drugs and technologies to diagnose and stage, and treatments to curtail the progression of and even cure, certain cancers, diseases of the heart and disorders of the circulatory system.